Challenges and advances in atomistic simulations of potassium and sodium ion channel gating and permeation

Ion channels are implicated in many essential physiological events such as electrical signal propagation and cellular communication. The advent of K+ and Na+ ion channel structure determination has facilitated numerous investigations of molecular determinants of their behaviour. At the same time, rapid development of computer hardware and molecular simulation methodologies has made computational studies of large biological molecules in all-atom representation tractable. The concurrent evolution of experimental structural biology with biomolecular computer modelling has yielded mechanistic details of fundamental processes unavailable through experiments alone, such as ion conduction and ion channel gating. This review is a short survey of the atomistic computational investigations of K+ and Na+ ion channels, focusing on KcsA and several voltage-gated channels from the K-V and Na-V families, which have garnered many successes and engendered several long-standing controversies regarding the nature of their structure-function relationship. We review the latest advancements and challenges facing the field of molecular modelling and simulation regarding the structural and energetic determinants of ion channel function and their agreement with experimental observations.